Artículos (Medicina)

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Recomendaciones conjuntas sobre el manejo del paciente con osteoporosis y/o fracturas por fragilidad durante y después de la pandemia por COVID-19 de la SEIOMM, SEFRAOS, SER, SEMI, SEGG, SEMG, SEMERGEN y SEEN
(Sociedad Española de Investigaciones Óseas y Metabolismo Mineral, 2022-06) Naves Díaz, Manuel; Peris Bernal, Pilar; Montoya García, María José; Casado Burgos, Enrique; Caeiro Rey, José Ramón; Guañabens Gay, Núria; Rozas Moreno, Pedro; Medicina; Instituto de Biomedicina de Sevilla (IBIS); CTS211: Metabolismo Cálcico, Hipertensión y Arteriosclerosis
La pandemia por COVID-19 ha impactado en la asistencia sanitaria de los pacientes con osteoporosis y fracturas por fragilidad. Algunas estrategias dirigidas a la protección contra el contagio del virus, como el distanciamiento social, han provocado unos cambios en los modelos asistenciales que no han sido homogéneos en todas las áreas. La necesidad de limitar el acceso a los centros sanitarios y los contagios ha impuesto la telemedicina. Son muchas las ventajas que puede ofrecer a profesionales y usuarios, convirtiéndose en una herramienta asistencial clave para poder asegurar el distanciamiento social. Asimismo, la consulta telemática puede tener aplicaciones adicionales en la práctica clínica habitual, ya que permite atender a pacientes con problemas de desplazamiento y solucionar de forma eficaz dudas y/o problemas relacionados con el tratamiento, por lo que podría ser especialmente útil para controlar el cumplimiento terapéutico. Sin embargo, para poder avanzar en una atención telemática más efectiva y segura, procurando siempre la mayor agilidad en las respuestas, ésta debería estar protocolizada. A partir de las recomendaciones conjuntas de la American Society for Bone and Mineral Research (ASBMR), American Association of Clinical Endocrinologists (AACE), European Calcified Tissue Society (ECTS) and National Osteoporosis Foundation (NOF), un grupo multidisciplinar de expertos de SEIOMM, junto con los de otras sociedades científicas (SEFRAOS, SER, SEMI, SEGG, SEMG, SEMERGEN y SEEN), ha elaborado este documento con el objetivo de establecer una serie de recomendaciones en el diagnóstico, tratamiento y seguimiento de los pacientes con osteoporosis y/o fractura por fragilidad osteoporótica durante y después de la pandemia por COVID-19 en España.
Role of rectal colonization by third-generation cephalosporin-resistant Enterobacterales on the risk of surgical site infection after hepato-pancreato-biliary surgery
(American Society for Microbiology, 2024-09-24) Rodríguez Fernández, Miguel; Trigo Rodríguez, Marta; Martínez Baena, Darío; Herrero, Rocío; Espíndola Gómez, Reinaldo; Martínez Pérez-Crespo, Pedro María; Gallego Vela, Alberto; Torres, Eva; García Aller, Ana Isabel; León, Eva M.; Corzo Delgado, Juan Enrique; Parra Membrives, Pablo; Merchante Gutiérrez, Nicolás; Cirugía; Medicina
The impact of third-generation cephalosporin-resistant Enterobacterales (3GCR-E) rectal colonization in the development of subsequent infection after surgery is controversial. In particular, there is a lack of data in the context of hepato-pancreato-biliary (HPB) surgery. The objective of this study was to assess the prevalence of 3GCR-E intestinal carriage among patients undergoing elective HPB resection surgery and its impact on the incidence and etiology of surgical site infections (SSIs). This retrospective cohort study (January 2016–December 2022) was performed at Valme University Hospital (Seville, Spain). The inclusion criteria included (i) 18 years of age or older, (ii) undergoing elective HPB resection surgery, and (iii) availability of a periprocedural surveillance rectal swab culture to detect 3GCR-E. The prevalence of 3GCR-E intestinal carriage at elective HPB resection surgery was assessed, as well as SSI incidence at 30 days and possible associated factors. Two hundred nine patients were included. Eleven (5.3%) patients were colonized by 3GCR-E at baseline. According to 3GCR-E carriage status, 6 (55%) of the carriers developed SSI, whereas this occurred in 50 (25%) of non-carriers (P = 0.033). Likewise, the rates of SSI caused specifically by 3GCR-E were 83% (5 of 6) in 3GCR-E carriers and 6% (3 of 50) in non-carriers (P < 0.001). After multivariate analyses, 3GCR-E colonization at the time of surgery was identified as an independent predictor for developing SSI (adjusted odds ratio 4.63, 95% confidence interval: 1.177–18.232, P = 0.028). Despite a low prevalence of 3GCR-E intestinal carriage at surgery, 3GCR-E rectal colonization is associated with a higher risk of SSI among patients undergoing elective HPB resection surgery, with most SSIs being caused by the colonizing bacteria.
Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort
(Elsevier, 2023-11-03) Herrera Hidalgo, Laura; Muñoz, Patricia; Álvarez Uría, Ana; Alonso Menchén, David; Luque Márquez, Rafael; Gutiérrez Carretero, Encarnación; López-Cortés, Luis E.; Alarcón González, Arístides de; Grupo de Apoyo al Manejo de la Endocarditis Infecciosa en España (GAMES Cohort Investigators); Lepe Jiménez, José Antonio; Araji Tiliani, Omar; Cueto López, Marina de; Cirugía; Medicina; European Union (UE); Instituto de Salud Carlos III; Subprograma Juan Rodes; CTS1134: Investigación Traslacional en la Fisiopatología Cardiovascular; CTS204: Biotecnología Aplicada al Estudio de Enfermedades Infecciosas
Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective.
Metabolic dysfunction-associated steatotic liver disease alters brain function and behavior: Insights from liver-targeted siRNA therapy
(Amer assoc advancement science, 2025-10-22) Cardoso Delgado, Teresa; Martín-Cuevas, Celia; Sánchez Hidalgo, Ana C.; Gil Gómez, Antonio; Rejano Gordillo, Claudia M.; Landa, Jon; Gallego Durán, Rocío; Romero Gómez, Manuel; Crespo Facorro, Benedicto; Martínez-Chantar, María Luz; Medicina; Fisiología; Psiquiatría; Instituto de Biomedicina de Sevilla (IBIS); CTS1086: Psiquiatría Traslacional
Metabolic dysfunction-associated steatotic liver disease (MASLD), a liver-centric condition, is associated with cognitive impairment and sensorimotor alterations. However, it remains unclear whether MASLD is sufficient to drive central nervous system deficits. Here, using diet-induced mouse models, we showed that MASLD was associated with alterations in social memory, sensorimotor processing, and hippocampal function, including decreased parvalbumin-positive interneurons, reduced dendritic spine density, and diminished dentate gyrus neurogenesis and neuronal differentiation. Then, we selectively modulated liver metabolism through N-acetylgalactosamine small interfering RNA (siRNA) therapy against Cyclin M4 (CNNM4), a magnesium transporter dysregulated in MASLD. Liver-specific intervention with siRNA-Cnnm4 reversed impaired social memory and sensorimotor processing in association with recovery of hippocampal synaptogenesis and mitochondrial function pathways, alongside activation of neurogenesis-associated transcriptional programs. Our findings demonstrate that liver pathology is sufficient to drive neurobehavioral and hippocampal dysfunction in MASLD. Hepatic-specific intervention restores brain function, strongly supporting the existence of a causal and therapeutically targetable liver-brain axis for MASLD-associated neurological complications.
Gastrostomies: experience and complications with three modalities in a tertiary centre over a 26-year period
(Frontiers Media, 2023-10-17) Piñar Gutiérrez, Ana; Serrano Aguayo, Pilar; Vázquez Gutiérrez, Rocío; García Rey, Silvia; González Navarro, Irene; Tatay Domínguez, Dolores; Socas Macías, María; Morales Conde, Salvador; García-Fernández, Francisco-José; Pereira Cunill, José Luis; García Luna, Pedro Pablo; Cirugía; Medicina
Objectives: To describe the complications associated with the different gastrostomy techniques [endoscopic (PEG), radiologic (PRG), and surgical (SG)] performed in the last 26 years in a terciary hospital. Methods: Retrospective observational study. Patients who underwent gastrostomy at the Virgen del Rocío University Hospital between 1995 and 2021 were included. For PEG, the PULL technique was performed until 2018 and subsequently the PUSH technique predominantly. For PRG, a pigtail catheter was used until 2003, a balloon catheter between 2003 and 2009, and a balloon catheter with gastropexy between 2015 and 2021. For SG, the conventional technique (CSG) was performed until 2009 and since then the laparoscopic assisted percutaneous gastrostomy (PLAG) technique. Descriptive analysis was performed obtaining the median and quartiles of the quantitative variables [P50 (P25-P75)] and the frequency for the qualitative variables [n (%)].The comparison of complications between patients who underwent different techniques was performed with Fisher’s test. Results: n = 1,070 (PEG = 608, PRG = 344, SG = 118). The three most frequent indications were head and neck tumors, neurological diseases and gastroesophageal tumors. The percentage of patients who had any complication was 48.9% (PEG-PULL), 23.7% (PEG-PUSH), 38.5% (pigtail PRG), 39.2% (balloon PRG), 29.7% (balloon with gastropexy PRG), 87.3% (CSG), and 41.26% (PLAG). 2 (0.18%) patients died from gastrostomy-related complications. 18(1.68%) presented with peritonitis and 5 (0.4%) presented with gastrocolic fistula. The rest of the complications were minor. Conclusion: Gastrostomy in any of its modalities is currently a safe procedure with a low rate of complications, most of which are minor.
Evaluation of alpha1 antitrypsin deficiency-associated mutations in people with cystic fibrosis
(MDPI, 2025-09-25) López-Campos Bodineau, José Luis; García Tamayo, Pedro; Girón, Maria Victoria; Delgado Pecellín, Isabel; Olveira, Gabriel; Carrasco, Laura; Quintana-Gallego, Esther; Medicina; Farmacología, Pediatría y Radiología
Background: Recent hypotheses suggest that mutations associated with alpha1 antitrypsin (AAT) deficiency (AATD) may influence the clinical presentation and progression of cystic fibrosis (CF). This study employs a longitudinal design to determine the prevalence of AATD mutations and assess their impact on CF. Methods: The study Finding AAT Deficiency in Obstructive Lung Diseases: Cystic Fibrosis (FADO-CF) is a retrospective cohort study evaluating people with CF from November 2020 to February 2024. On the date of inclusion, serum levels of AAT were measured and a genotyping of 14 mutations associated with AATD was performed. Historical information, including data on exacerbations, microbiological sputum isolations, and lung function, was obtained from the medical records, aiming at a temporal lag of 10 years. Results: The sample consisted of 369 people with CF (40.9% pediatrics). Of these, 58 (15.7%) cases presented at least one AATD mutation. The AATD allelic combinations identified were PI*MS in 47 (12.7%) cases, PI*MZ in 5 (1.4%) cases, PI*SS in 3 (0.8%) cases, PI*SZ in 2 (0.5%) cases, and PI*M/Plowell in 1 (0.3%) case. The optimal cutoff value for AAT levels to detect AATD-associated mutation carriers was 129 mg/dL in the overall cohort (sensitivity of 73.0%; specificity 69.2%) and 99.5 mg/dL when excluding PI*MS cases (sensitivity 98.0%; specificity 90.9%), highlighting the need for lower thresholds in clinically severe genotypes to improve case detection. The number of mild exacerbations during the follow-up appeared to be associated with AATD mutations. Conclusions: AATD mutations are prevalent in CF and may impact certain clinical outcomes. If systematic screening was to be planned, we recommend considering the proposed cut-off points to select the population for genetic studies.
Utility of Telehealth Platforms Applied to Burns Management: A Systematic Review
(MDPI, 2023-02-10) García Díaz, Antonio; Vilardell Roig, Lluis; Novillo Ortiz, David; Gacto Sánchez, Purificación; Pereyra-Rodríguez, José-Juan; Saigi Rubio, Francesc; Cirugía; Medicina; World Health Organization
The financial burden of burn injuries has a considerable impact on patients and healthcare systems. Information and Communication Technologies (ICTs) have demonstrated their utility in the improvement of clinical practice and healthcare systems. Because referral centres for burn injuries cover large geographic areas, many specialists must find new strategies, including telehealth tools for patient evaluation, teleconsultation, and remote monitoring. This systematic review was performed according to PRISMA guidelines. PubMed, Cochrane, Medline, IBECS, and LILACS were the search engines used. Systematic reviews, meta-analyses, clinical trials, and observational studies were included in the study search. The protocol was registered in PROSPERO with the number CRD42022361137. In total, 37 of 185 studies queried for this study were eligible for the systematic review. Thirty studies were comparative observational studies, six were systematic reviews, and one was a randomised clinical trial. Studies suggest that telehealth allows better perception of triage, more accurate estimation of the TBSA, and resuscitation measures in the management of acute burns. In addition, some studies assess that TH tools are equivalent to face-to-face outpatient visits and cost-efficient because of transport savings and unnecessary referrals. However, more studies are required to provide significant evidence. However, the implementation of telehealth should be specifically adapted to each territory.
Evaluation of lung parenchyma, blood vessels, and peripheral blood lymphocytes as a potential source of acute phase reactants in patients with COPD
(Dove Press, 2019-03-18) Arellano Orden, Elena; Calero, Carmen; López Ramírez, Cecilia; Sánchez López, Verónica; López-Villalobos, José Luis; Abad Arranz, María; Blanco Orozco, Ana Isabel; Otero Candelera, Remedios; López-Campos Bodineau, José Luis; Cirugía; Medicina; Asociación de Neumología y Cirugía Torácica del Sur (NEUMOSUR); Instituto de Salud Carlos III; Gobierno de España; Red de Biobanco
Background: Previous studies have shown that the arterial wall is a potential source of inflammatory markers in COPD. Here, we sought to compare the expression of acute phase reactants (APRs) in COPD patients and controls both at the local (pulmonary arteries and lung parenchyma) and systemic (peripheral blood leukocytes and plasma) compartments. Methods: Consecutive patients undergoing elective surgery for suspected primary lung cancer were eligible for the study. Patients were categorized either as COPD or control group based on the spirometry results. Pulmonary arteries and lung parenchyma sections, peripheral blood leukocytes, and plasma samples were obtained from all participants. Gene expression levels of C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2, and SAA4) were evaluated in tissue samples and peripheral blood leukocytes by reverse transciption-PCR. Plasma CRP and SAA protein levels were measured by enzyme-linked immunosorbent assays. Proteins were evaluated in paraffin-embedded lung tissues by immunohistochemistry. Results: A total of 40 patients with COPD and 62 controls were enrolled. We did not find significant differences in the gene expression between COPD and control group. Both CRP and SAA were overexpressed in the lung parenchyma compared with pulmonary arteries and peripheral blood leukocytes. The expression of SAA was significantly higher in the lung parenchyma than in the pulmonary artery (2-fold higher for SAA1 and SAA4, P=0.015 and P<0.001, respectively; 8-fold higher for SAA2, P<0.001) and peripheral blood leukocytes (16-fold higher for SAA1, 439-fold higher for SAA2, and 5-fold higher for SAA4; P<0.001). No correlation between plasma levels of inflammatory markers and their expression in the lung and peripheral blood leukocytes was observed. Conclusions: The expression of SAA in lung parenchyma is higher than in pulmonary artery and peripheral blood leukocytes. Notably, no associations were noted between lung expression of APRs and their circulating plasma levels, making the leakage of inflammatory proteins from the lung to the bloodstream unlikely. Based on these results, other potential sources of systemic inflammation in COPD (eg, the liver) need further scrutiny.
Proyecto CUDERMA: Consenso Delphi de los indicadores de calidad para la certificación de las unidades de dermatología de atención en dermato-oncología
(Elsevier, 2023-02-19) Martínez de Espronceda Ezquerro, I.; Podlipnik, S.; Cañueto, J.; de la Cuadra-Grande, A.; Serra-Guillén, C.; Moreno Ramírez, David; Ferrándiz Pulido, Lara; Arias-Santiago, S.; Multidisciplinary Grp; Consensus Grp; Medicina; (Gerencia Regional de Salud de Castilla y Leon) from ISCIII; Abbvie; Programa CERCA de la Generalitat de Catalunya (España); Comisión Europea, en el marco del Sexto Programa Marco, Diagnoptics; Comisión Europea en el marco del Programa Marco HORIZON2020, iTobos; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Fondo de Investigaciones Sanitarias (España); Fundación Científica de la Asociación Española Contra el Cáncer, España; Institu-tuto de Salud Carlos III (ISCIII) Centro de Investigación Biomédica en Enfermedades Raras (CIBER) - ISCII; ISCII-Subdirección General de Evaluación; Instituto Nacional del Cáncer de los Estados Unidos Instituto Nacional de Salud; Programa de Intensificación del ISCIII
Los indicadores de calidad son una herramienta clave como garantía de calidad y homogenización de la asistencia sanitaria. En este contexto, la Academia Española de Dermatología y Venereología ha diseñado el proyecto Certificación de unidades de dermatología (CUDERMA), una iniciativa que busca definir indicadores de calidad para certificar unidades de dermatología en distintos ámbitos, entre los que se seleccionaron psoriasis y dermato-oncología de forma inicial. Este estudio tuvo por objetivo consensuar los aspectos a evaluar por los indicadores, siguiendo un proceso estructurado para la revisión bibliográfica y elaboración de un set preliminar de indicadores, revisado por un grupo multidisciplinar de expertos, para su evaluación mediante un Consenso Delphi. Un panel de 28 dermatólogos evaluó los indicadores y los clasificó como «básicos» o «de excelencia», generando un conjunto de 84 indicadores consensuados que serán estandarizados para diseñar la norma para certificar las unidades de dermato-oncología.
Mediterranean diet and quality of life: Baseline cross-sectional analysis of the PREDIMED-PLUS trial
(Public Library of Science (PLoS), 2018-06-18) Galilea-Zabalza, Iñigo; Buil-Cosiales, Pilar; Salas Salvado, Jordi; Toledo, Estefanía; Ortega-Azorín, Carolina; Díez-Espino, Javier; Ortega Calvo, Manuel; Martínez-González, Miguel Ángel; Santos Lozano, José Manuel; Urbano Fernández, Victor; PREDIMED-PLUS Study Investigators; Medicina; Instituto de Salud Carlos III; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía
We assessed if a 17-item score capturing adherence to a traditional Mediterranean diet (MedDiet) was associated with better health-related quality of life among older Spanish men and women with overweight or obesity harboring the metabolic syndrome. We analyzed baseline data from 6430 men and women (age 55–70 years) participating in the PREDIMED-Plus study. PREDIMED-Plus is a multi-centre randomized trial testing an energy-restricted MedDiet combined with promotion of physical activity and behavioral therapy for primary cardiovascular prevention compared to a MedDiet alone. Participants answered a 36-item questionnaire about health-related quality of life (HRQoL) and a 17-item questionnaire that assessed adherence to an MedDiet. We used ANCOVA and multivariable-adjusted linear regression models to compare baseline adjusted means of the quality of life scales according to categories of adherence to the MedDiet. Higher adherence to the MedDiet was independently associated with significantly better scores in the eight dimensions of HRQoL. Adjusted differences of > = 3 points between the highest and the lowest dietary adherence groups to the MedDiet were observed for vitality, emotional role, and mental health and of > = 2 points for the other dimensions. In conclusion, this study shows a positive association between adherence to a MedDiet and several dimensions of quality of life.
Dual-Chamber Pacing With Closed Loop Stimulation in Recurrent Reflex Vasovagal Syncope: The Spain Study
(American College of Cardiology, 2017-09-25) Barón-Esquivias, Gonzalo; Morillo, Carlos A.; Moya Mitjans, Ángel; Martínez Alday, Jesús; Ruiz Granell, Ricardo; Lacunza Ruiz, Javier; García Civera, Roberto; Gutiérrez Carretero, Encarnación; Romero Garrido, Rafael; Cirugía; Medicina; CTS1134: Investigación Traslacional en la Fisiopatología Cardiovascular
Background: Pacing in vasovagal syncope remains controversial. Objectives: The authors evaluated dual-chamber pacing with closed loop stimulation (DDD-CLS) in patients with cardioinhibitory vasovagal syncope. Methods: This randomized, double-blind, controlled study included Canadian and Spanish patients age ≥40 years, with high burden syncope (≥5 episodes, ≥2 episodes in the past year), and a cardioinhibitory head-up tilt test (bradycardia <40 beats/min for 10 s or asystole >3 s). Patients were randomized to either DDD-CLS pacing for 12 months followed by sham DDI mode pacing at 30 pulses/min for 12 months (group A), or sham DDI mode for 12 months followed by DDD-CLS pacing for 12 months (group B). Patients in both arms crossed-over after 12 months of follow-up or when a maximum of 3 syncopal episodes occurred within 1 month. Results: A total of 46 patients completed the protocol; 22 were men (47.8%), and mean age was 56.30 ± 10.63 years. The mean number of previous syncopal episodes was 12 (range 9 to 20). The proportion of patients with ≥50% reduction in the number of syncopal episodes was 72% (95% confidence interval [CI]: 47% to 90%) with DDD-CLS compared with 28% (95% CI: 9.7% to 53.5%) with sham DDI mode (p = 0.017). A total of 4 patients (8.7%) had events during DDD-CLS and 21 (45.7%) during sham DDI (hazard ratio: 6.7; 95% CI: 2.3 to 19.8). Kaplan-Meier curve was significantly different between groups in time to first syncope: 29.2 months (95% CI: 15.3 to 29.2 months) versus 9.3 months (95% CI: 6.21 months, NA; p < 0.016); odds ratio: 0.11 (95% CI: 0.03 to 0.37; p < 0.0001). Conclusions: DDD-CLS pacing significantly reduced syncope burden and time to first recurrence by 7-fold, prolonging time to first syncope recurrence in patients age ≥40 years with head-up tilt test–induced vasovagal syncope compared with sham pacing. (Closed Loop Stimulation for Neuromediated Syncope.
Impact of Low-Density Lipoprotein Cholesterol Target on Atherosclerotic Ischemic Stroke in Asian Patients
(Korean Stroke Society, 2025-09-02) Castilla Guerra, Luis; Fernández Moreno, María del Carmen; Carmona Nimo, Eduardo; Medicina
The PNPLA3 genetic variant rs738409 influences the progression to cirrhosis in hiv/hepatitis c virus coinfected patients
(Public Library of Science (PLoS), 2016-12-14) Núñez-Torres, Rocío; Macías Sánchez, Juan; Mancebo, María; Frías, Mario; Dolci, Giovanni; Téllez, Francisco; Merchante Gutiérrez, Nicolás; Gómez Mateos, Jesús María; Pineda Vergara, Juan Antonio; Real Navarrete, Luis Miguel; Medicina; Bioquímica Médica y Biología Molecular e Inmunología; Junta de Andalucía; Gobierno de España; Instituto de Salud Carlos III; Ministerio de Economia, Industria y Competitividad (MINECO). España
Contradictory data about the impact of the rs738409 steatosis-related polymorphism within PNPLA3geneonliver fibrosis progression in HIV/hepatitis C virus (HIV/HCV)-coinfected patients have been reported. Our objective was to test whether this, and other polymor phisms previously related to fatty liver disease in HIV infection linked to SAMM50 or LPPR4 genes, influence liver fibrosis progression in HIV/HCV-coinfected individuals. Three hun dred andthirty two HIV/HCV-coinfected patients who consecutively attended four Spanish university hospitals from November 2011 to July 2013 were included. A liver stiffness cut-off of 14.6 kPa, as determined by transient elastography, was used to diagnose cirrhosis. Liver stiffness progression was studied in 171 individuals who had two available LS determina tions without anti-HCV treatment between them. Moreover, 28 HIV/HCV-coinfected patients whounderwent liver transplant, as well as 19 non-cirrhotic coinfected individuals used as controls, were included in an additional study. Only rs738409 was associated with cirrhosis: 45 (29.6%) of 152 Gallele carriers versus 36 (20.0%) of 180 CC carriers showed cirrhosis (multivariate p = 0.018; adjusted odds ratio = 1.98; 95% confidence interval = 1.123.50). Also, 21 (30.4%) of 69 Gallele carriers versus 16 (15.7%) of 102 CC patients showed signifi cant liver stiffness progression (adjusted p-value = 0.015; adjusted odds ratio = 2.89; 95% confidence interval = 1.236.83). Finally, the proportion of rs738409 G allele carriers was significantly higher in transplanted individuals than in controls (p = 0.044, odds ratio = 3.43; 95%confidence interval = 1.0111.70). Our results strongly suggest that the rs738409 poly morphism is associated with liver fibrosis progression in HIV/HCV-coinfected patients.
Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: the GR@ACE Project
(Elsevier Inc.; WILEY, 2019-10) Moreno-Grau, Sonia; de Rojas, Itziar; Hernández, Isabel; Quintela, Inés; Montrreal, Laura; Alegret, Montserrat; Pineda Vergara, Juan Antonio; Macías Sánchez, Juan; Mir Rivera, Pablo; Real Navarrete, Luis Miguel; Ruiz, A.; GR@ACE consortium; Degesco Consortium; Alzheimer's disease neuroimaging initiative; Labrador Espinosa, Miguel Ángel; Periñan Tocino, Maria Teresa; Medicina; Bioquímica Médica y Biología Molecular e Inmunología; Agencia IDEA (Consejeria de Innovacion, Junta de Andalucia); AGES; Neuroimagen de la Enfermedad de Alzheimer (ADNI) (Institutos Nacionales de Salud); Fundación para el Descubrimiento de Fármacos para el Alzheimer; Investigación sobre el Alzheimer en el Reino Unido; Biogen; Fundación de Investigación Biomédica; Compañía Bristol-Myers Squibb; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM); Consejeria de Salud de la Junta de Andalucia; Corporacion Tecnologica de Andalucia; CurePSP Foundation; DOD ADNI (Departamento de Defensa); Iniciativa sobre medicamentos innovadores de la Unión Europea/EFPIA, proyecto conjunto ADAPTED; Iniciativa sobre medicamentos innovadores de la Unión Europea/EFPIA, proyecto conjunto MOPEAD; Fondo Europeo de Desarrollo Regional (FEDER-"Una manera de Hacer Europa"); Ministerio Federal de Educación e Investigación de Alemania (BMBF): Red de Competencia en Demencia (CND); ISCIII (Instituto de Salud Carlos III)-Subdireccion General de Evaluacion; Lille University Hospital; Centro de Enfermedad de Alzheimer de Mayo Clinic; Medical Research Council; Ministerio de Educacion y Ciencia (Gobierno de Espana); National Alzheimer's Coordinating Center; Instituto Nacional sobre el Envejecimiento (Centro de Enfermedad de Alzheimer de Arizona); NHLBI; NIA; NIA Division of Neuroscience; NINDS; Las PYME como parte de InnoMed (Medicamentos Innovadores en Europa) - Unión Europea del Sexto Programa Marco, prioridad FP6-2004-LIFESCIHEALTH-5; Wellcome Trust
Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series.
High rate of major drug–drug interactions of lopinavir–ritonavir for COVID-19 treatment
(Nature Publishing Group; Nature Portfolio, 2020-12-01) Macías Sánchez, Juan; Pinilla, Ana; Lao-Dominguez, Francisco A.; Corma, Anaïs; Contreras Macías, Enrique; González-Serna Martín, Manuel Alejandro; Morillo Verdugo, Ramón Alejandro; Real Navarrete, Luis Miguel; Pineda Vergara, Juan Antonio; Medicina; Fisiología; Farmacología; Bioquímica Médica y Biología Molecular e Inmunología
The impact of drug–drug interactions (DDI) between ritonavir-boosted lopinavir (LPV-r) to treat patients with coronavirus disease 2019 (COVID-19) and commonly used drugs in clinical practice is not well-known. Thus, we evaluated the rate and severity of DDI between LPV-r for COVID-19 treatment and concomitant medications. This was a cross-sectional study including all individuals diagnosed of SARS-CoV-2 infection treated with LPV-r and attended at a single center in Southern Spain (March 1st to April 30th, 2020). The frequency [95% confidence interval (95% CI)] of potential and major DDI were calculated. Overall, 469 patients were diagnosed of COVID-19, 125 (27%) of them were prescribed LPV-r. LPV-r had potential DDI with concomitant medications in 97 (78%, 95% CI 69–85%) patients, and in 33 (26%, 95% CI 19–35%) individuals showed major DDI. Twelve (36%) patients with major DDI and 14 (15%) individuals without major DDI died (p = 0.010). After adjustment, only the Charlson index was independently associated with death [adjusted OR (95% CI) for Charlson index ≥ 5: 85 (10–731), p < 0.001]. LPV-r was discontinued due to side effects in 31 (25%) patients. Management by the Infectious Diseases Unit was associated with a lower likelihood of major DDI [adjusted odds ratio (95% CI): 0.14 (0.04–0.53), p = 0.003). In conclusion, a high frequency of DDI between LPV-r for treating COVID-19 and concomitant medications was found, including major DDI. Patients with major DDI showed worse outcomes, but this association was explained by the older age and comorbidities. Patients managed by the Infectious Diseases Unit had lower risk of major DDI.
How do women living with HIV experience menopause? Menopausal symptoms, anxiety and depression according to reproductive age in a multicenter cohort
(Biomed central LTD, 2021-05-28) Suarez-Garcia, I.; Alejos, B.; Perez-Elias, M.J.; Iribarren, J.A.; Hernando, A.; Ramirez, M.; Hernando, V.; CoRIS Cohort; Pineda Vergara, Juan Antonio; Macías Sánchez, Juan; Merchante Gutiérrez, Nicolás; Real Navarrete, Luis Miguel; González-Serna Martín, Manuel Alejandro; Pousada, Guillermo; Medicina; Fisiología; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Instituto de Salud Carlos III a través de la Red Temática de Investigación Cooperativa en Asdi, Plan Nacional I+D+I; ISCIII-Subdireccion General de Evaluacion; Accion Estrategica en Salud Intramural
Background: To estimate the prevalence and severity of menopausal symptoms and anxiety/depression and to assess the differences according to menopausal status among women living with HIV aged 45-60 years from the cohort of Spanish HIV/AIDS Research Network (CoRIS). Methods: Women were interviewed by phone between September 2017 and December 2018 to determine whether they had experienced menopausal symptoms and anxiety/depression. The Menopause Rating Scale was used to evaluate the prevalence and severity of symptoms related to menopause in three subscales: somatic, psychologic and urogenital; and the 4-item Patient Health Questionnaire was used for anxiety/depression. Logistic regression models were used to estimate odds ratios (ORs) of association between menopausal status, and other potential risk factors, the presence and severity of somatic, psychological and urogenital symptoms and of anxiety/depression. Results: Of 251 women included, 137 (54.6%) were post-, 70 (27.9%) peri- and 44 (17.5%) pre-menopausal, respectively. Median age of onset menopause was 48 years (IQR 45-50). The proportions of pre-, peri- and post-menopausal women who had experienced any menopausal symptoms were 45.5%, 60.0% and 66.4%, respectively. Both peri- and post-menopause were associated with a higher likelihood of having somatic symptoms (aOR 3.01; 95% CI 1.38-6.55 and 2.63; 1.44-4.81, respectively), while post-menopause increased the likelihood of having psychological (2.16; 1.13-4.14) and urogenital symptoms (2.54; 1.42-4.85). By other hand, post-menopausal women had a statistically significant five-fold increase in the likelihood of presenting severe urogenital symptoms than pre-menopausal women (4.90; 1.74-13.84). No significant differences by menopausal status were found for anxiety/depression. Joint/muscle problems, exhaustion and sleeping disorders were the most commonly reported symptoms among all women. Differences in the prevalences of vaginal dryness (p = 0.002), joint/muscle complaints (p = 0.032), and sweating/flush (p = 0.032) were found among the three groups. Conclusions: Women living with HIV experienced a wide variety of menopausal symptoms, some of them initiated before women had any menstrual irregularity. We found a higher likelihood of somatic symptoms in peri- and post-menopausal women, while a higher likelihood of psychological and urogenital symptoms was found in post-menopausal women. Most somatic symptoms were of low or moderate severity, probably due to the good clinical and immunological situation of these women.
Plasmacytoid and cd141+ myeloid dendritic cells cooperation with cd8+ t cells in lymph nodes is associated with hiv control
(Wiley, 2025-09-12) Vitallé, Joana; Bachiller, Sara; Domínguez-Molina, Beatriz; Moysi, Eirini; Ferrando Martínez, Sara; Camacho Sojo, María Inés; Ostos Marcos, Francisco José; Rafii-El-Idrissi Benhnia, Mohammed; López Cortés, Luis Fernando; Ruiz Mateos Carmona, Ezequiel; Medicina; Bioquímica Médica y Biología Molecular e Inmunología; Química Física; FQM206: Grupo de Cinética del Profesor Rodríguez Velasco
Dendritic cells (DC) are known to modulate antiviral immune responses; however, the knowledge about the role of different DC subsets in antiviral T cell priming in human tissues remains uncompleted. In the context of HIV infection, we determined the phenotype and location of plasmacytoid and CD141+ myeloid DCs (pDCs and mDCs) in lymph nodes of people living with HIV (PLWH). We found an interaction between pDCs and CD141+ mDCs with CD8+ T cells, being associated with participants’ viral levels in blood and tissue. Moreover, we demonstrated a higher and more polyfunctional superantigen- and HIV-specific CD8+ T cell response after the coculture with Toll-like receptor (TLR)-primed pDCs and CD141+ mDCs. Last, we showed the potential of programmed cell death-1 (PD-1) blocking using pembrolizumab to further increase antigen-specific CD8+ T cell response along with TLR agonists. Therefore, these results showed a cooperation between pDCs, CD141+ mDCs and CD8+ T cells in lymph nodes of PLWH, which is associated with higher HIV control, highlighting the importance of DC subsets crosstalk to achieve a more potent anti-HIV response and support the use of DC-based immunotherapies for HIV control.
Nutritional and morphofunctional assessment in a cohort of adults living with cystic fibrosis with or without pancreatic exocrine and/or endocrine involvement
(Mdpi Ag, 2025-06-20) Piñar-Gutiérrez, Ana; Pereira Cunill, José Luis; Jiménez Sánchez, Andrés; García-Rey, Silvia; Roque-Cuéllar, María del Carmen; Martínez-Ortega, Antonio J.; Medicina
Objectives: To describe the results of nutritional and morphofunctional assessment in a cohort of adults with cystic fibrosis; to evaluate differences in nutritional status between patients with and without exocrine and/or endocrine pancreatic involvement. Methods: Cross-sectional study: A cohort of adults with cystic fibrosis evaluated in a multidisciplinary unit was analyzed. Pancreatic status was examined, and malnutrition was diagnosed according to GLIM criteria. Morphofunctional assessment consisted of nutritional ultrasound, bioelectrical impedance, handgrip dynamometry, and anthropometry. Qualitative variables are expressed as n (%), quantitative variables as median (IQR). For group comparisons, Fisher’s exact test was used for qualitative variables and the non-parametric median comparison test for quantitative variables. Results: n = 101 participants were recruited, of whom 44 (43.6%) were women. Median age was 33 (25–40.5) years. A total of 64 participants (63.4%) had exocrine pancreatic insufficiency (EPI), 44 (43.6%) had endocrine pancreatic insufficiency, and 28 (27.7%) had cystic fibrosis-related diabetes (CFRD). Median BMI was 23.4 (20.1–24.89) kg/m2. A total of 48 patients (47.5%) were malnourished. Males with EPI had a higher prevalence of undernourishment than those without (56.4% vs. 16.7%, p = 0.005), but not women. CFRD patients displayed no differences in morphofunctional assessment. Conclusions: Almost half the sample was undernourished using GLIM criteria. Males with exocrine pancreatic insufficiency had worse nutritional status. Endocrine pancreatic involvement did not affect nutritional status.
MicroRNA Profile of HCV Spontaneous Clarified Individuals, Denotes Previous HCV Infection
(MDPI, 2019-06-19) Brochado-Kith, Oscar; Gómez Sanz, Alicia; Real Navarrete, Luis Miguel; Crespo García, Javier; Ryan Murúa, Pablo; Macías Sánchez, Juan; Pineda Vergara, Juan Antonio; Fernández-Rodríguez, Amanda; Bioquímica Médica y Biología Molecular e Inmunología; Medicina; Instituto de Salud Carlos III (Subdireccion General de Evaluacion) Fondo de Investigacion Sanitaria (FIS); Proyectos Integrados de Excelencia
Factors involved in the spontaneous cleareance of a hepatitis C (HCV) infection are related to both HCV and the interaction with the host immune system, but little is known about the consequences after a spontaneous resolution. The main HCV extrahepatic reservoir is the peripheral blood mononuclear cells (PBMCs), and their transcriptional profile provides us information of innate and adaptive immune responses against an HCV infection. MicroRNAs regulate the innate and adaptive immune responses, and they are actively involved in the HCV cycle. High Throughput sequencing was used to analyze the miRNA profiles from PBMCs of HCV chronic naïve patients (CHC), individuals that spontaneously clarified HCV (SC), and healthy controls (HC). We did not find any differentially expressed miRNAs between SC and CHC. However, both groups showed similar expression differences (21 miRNAs) with respect to HC. This miRNA signature correctly classifies HCV-exposed (CHC and SC) vs. HC, with the has-miR-21-3p showing the best performance. The potentially targeted molecular pathways by these 21 miRNAs mainly belong to fatty acids pathways, although hippo signaling, extracellular matrix (ECM) interaction, proteoglycans-related, and steroid biosynthesis pathways were also altered. These miRNAs target host genes involved in an HCV infection. Thus, an HCV infection promotes molecular alterations in PBMCs that can be detected after an HCV spontaneous resolution, and the 21-miRNA signature is able to identify HCV-exposed patients (either CHC or SC).
Effectiveness of the combination elvitegravir/cobicistat/tenofovir/emtricitabine (EVG/COB/TFV/FTC) plus darunavir among treatment-experienced patients in clinical practice: A multicentre cohort study
(Biomed Central Ltd, 2020-07-20) López Cortés, Luis Fernando; Macías Sánchez, Juan; Merchante Gutiérrez, Nicolás; Real Navarrete, Luis Miguel; González-Serna Martín, Manuel Alejandro; Suárez-García, Inés; Moreno, Cristina; Ruiz-Algueró, Marta; Pérez-Elías, María Jesús; Navarro, Marta; Díez Martínez, Marcos; Medicina; Bioquímica Médica y Biología Molecular e Inmunología; Fisiología; Instituto de Salud Carlos III; Gobierno de España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
Background: The aim of this study was to investigate the effectiveness and tolerability of the combination elvitegra vir/cobicistat/tenofovir/emtricitabine plus darunavir (EVG/COB/TFV/FTC + DRV) in treatment experienced patients from the cohort of the Spanish HIV/AIDS Research Network (CoRIS). Methods: Treatment experienced patients starting treatment with EVG/COB/TFV/FTC + DRV during the years 2014–2018 and with more than 24 weeks of follow up were included. TFV could be administered either as tenofovir disoproxil fumarate or tenofovir alafenamide. We evaluated virological response, defined as viral load (VL) < 50 copies/ ml and < 200 copies/ml at 24 and 48 weeks after starting this regimen, stratified by baseline VL (< 50 or ≥ 50 copies/ml at the start of the regimen). Results: We included 39 patients (12.8% women). At baseline, 10 (25.6%) patients had VL < 50 copies/ml and 29 (74.4%) had ≥ 50 copies/ml. Among patients with baseline VL < 50 copies/ml, 85.7% and 80.0% had VL < 50 copies/ml at 24 and 48 weeks, respectively, and 100% had VL < 200 copies/ml at 24 and 48 weeks. Among patients with baseline VL ≥ 50 copies/ml, 42.3% and 40.9% had VL < 50 copies/ml and 69.2% and 68.2% had VL < 200 copies/ml at 24 and 48 weeks. During the first 48 weeks, no patients changed their treatment due to toxicity, and 4 patients (all with base line VL ≥ 50 copies/ml) changed due to virological failure. Conclusions: EVG/COB/TFV/FTC + DRV was well tolerated and effective in treatment experienced patients with undetectable viral load as a simplification strategy, allowing once daily, two pill regimen with three antiretroviral drug classes. Effectiveness was low in patients with detectable viral loads.

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